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GeneBe

4-101025907-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_000944.5(PPP3CA):c.1524C>T(p.Asn508=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000294 in 1,595,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

PPP3CA
NM_000944.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.29
Variant links:
Genes affected
PPP3CA (HGNC:9314): (protein phosphatase 3 catalytic subunit alpha) Enables several functions, including ATPase binding activity; calmodulin binding activity; and calmodulin-dependent protein phosphatase activity. Involved in several processes, including calcineurin-NFAT signaling cascade; peptidyl-serine dephosphorylation; and response to calcium ion. Located in several cellular components, including cytosol; dendritic spine; and nucleoplasm. Part of calcineurin complex. Colocalizes with cytoplasmic side of plasma membrane. Implicated in developmental and epileptic encephalopathy 91. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-101025907-G-A is Benign according to our data. Variant chr4-101025907-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1619007.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAdExome at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PPP3CANM_000944.5 linkuse as main transcriptc.1524C>T p.Asn508= synonymous_variant 14/14 ENST00000394854.8
PPP3CANM_001130691.2 linkuse as main transcriptc.1494C>T p.Asn498= synonymous_variant 13/13
PPP3CANM_001130692.2 linkuse as main transcriptc.1368C>T p.Asn456= synonymous_variant 12/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PPP3CAENST00000394854.8 linkuse as main transcriptc.1524C>T p.Asn508= synonymous_variant 14/141 NM_000944.5 P3Q08209-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000269
AC:
4
AN:
148602
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000743
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000675
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000443
AC:
11
AN:
248074
Hom.:
0
AF XY:
0.0000596
AC XY:
8
AN XY:
134274
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000274
Gnomad SAS exome
AF:
0.0000330
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000297
AC:
43
AN:
1447388
Hom.:
0
Cov.:
35
AF XY:
0.0000417
AC XY:
30
AN XY:
719774
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000227
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000234
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000245
Gnomad4 OTH exome
AF:
0.0000672
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000269
AC:
4
AN:
148602
Hom.:
0
Cov.:
31
AF XY:
0.0000554
AC XY:
4
AN XY:
72192
show subpopulations
Gnomad4 AFR
AF:
0.0000743
Gnomad4 AMR
AF:
0.0000675
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 18, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
13
Dann
Benign
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756110649; hg19: chr4-101947064; COSMIC: COSV59925308; API